Recanalization of previously coiled aneurysms remains a major drawback of endovascular aneurysm therapy. We performed a prospective single arm trial to provide early initial data regarding the safety and angiographic durability of a new coil technology, the Axium MicroFX Polyglycolic/polylactic acid (PGLA) coil, which was designed to lower recanalization rates.
Fifteen patients (16 aneurysms) were prospectively enrolled. Demographic and peri-procedural data were collected. Angiographic images of the initial coil embolization and three to six month follow-up angiographic images underwent blinded evaluation.
Seven (47%) SAH and eight (53%) elective patients were enrolled. Blinded evaluation of the initial embolization demonstrated that 5/16 (31%) aneurysms achieved Raymond grade 1, 5/16 (31%) grade 2 and 6/16 (38%) grade 3. Three to six month angiography was obtained in 12/15 patients (80%); two patients expired (1 SAH, 1 elective) and one was lost to follow-up (SAH). All patients who underwent follow-up angiography had a mRS ≤1. Blinded evaluation of embolization demonstrated 7/13 aneurysms (54%) improved in Raymond grading, five (38%) were stable and one aneurysm (8%) worsened. One patient developed an asymptomatic peri-aneurysmal parent vessel stenosis.
Axium MicroFX coils appear to be safe, though the small number of patients in this series obviates comparative analysis with other series. Further studies are needed with more patients to compare the angiographic durability of Axium MicroFX coils to other coils.
coiling, PGLA, safety, durability, Raymond grade, recanalization, Axium MicroFX
Current challenges in adhesive dentistry include over-hydrophilic bonding formulations, which facilitate water percolation through the hybrid layer and result in unreliable bonded interfaces. This study introduces nanogel-modified adhesives as a way to control the material’s hydrophobic character without changing the basic monomer formulation (keeping water-chasing capacity and operatory techniques unaltered). Nanogel additives of varied hydrophobicity were synthesized in solution, rendering 10- to 100-nm-sized particles. A model BisGMA/HEMA solvated adhesive was prepared (control), to which reactive nanogels were added. The increase in adhesive viscosity did not impair solvent removal by air-thinning. The degree of conversion in the adhesive was similar between control and nanogel-modified materials, while the bulk dry and, particularly, the wet mechanical properties were significantly improved through nanogel-based network reinforcement and reduced water solubility. As preliminary validation of this approach, short-term micro-tensile bond strengths to acid-etched and primed dentin were significantly enhanced by nanogel inclusion in the adhesive resins.
adhesives; polymers; restorative dentistry; materials science(s); water; nanoparticles
This study describes the clinical characteristics and corticosteroid responsiveness of children with difficult asthma (DA). We hypothesised that complete corticosteroid responsiveness (defined as improved symptoms, normal spirometry, normal exhaled nitric oxide fraction (FeNO) and no bronchodilator responsiveness (BDR <12%)) is uncommon in paediatric DA.
We report on 102 children, mean±SD age 11.6±2.8 yrs, with DA in a cross-sectional study. 89 children underwent spirometry, BDR and FeNO before and after 2 weeks of systemic corticosteroids (corticosteroid response study). Bronchoscopy was performed after the corticosteroid trial.
Of the 102 patients in the cross-sectional study, 88 (86%) were atopic, 60 (59%) were male and 52 (51%) had additional or alternative diagnoses. Out of the 81 patients in the corticosteroid response study, nine (11%) were complete responders. Of the 75 patients with symptom data available, 37 (49%) responded symptomatically, which was less likely if there were smokers in the home (OR 0.31, 95% CI 0.02–0.82). Of the 75 patients with available spirometry data, 35 (46%) had normal spirometry, with associations being BAL eosinophilia (OR 5.43, 95% CI 1.13–26.07) and high baseline forced expiratory volume in 1 s (FEV1) (OR 1.08, 95% CI 1.02–1.12). Of these 75 patients, BDR data were available in 64, of whom 36 (56%) had <12% BDR. FeNO data was available in 70 patients, of whom 53 (75%) had normal FeNO. Airflow limitation data was available in 75 patients, of whom 17 (26%) had persistent airflow limitation, which was associated with low baseline FEV1 (OR 0.93, 95% CI 0.90–0.97).
Only 11% of DA children exhibited complete corticosteroid responsiveness. The rarity of complete corticosteroid responsiveness suggests alternative therapies are needed for children with DA.
Corticosteroid responsiveness; difficult asthma; eosinophil; nitric oxide; paediatric asthma
The proto-oncogenic protein c-Myb is an essential regulator of hematopoiesis and is frequently deregulated in hematological diseases such as lymphoma and leukemia. To gain insight into the mechanisms underlying the aberrant expression of c-Myb in myeloid leukemia, we analyzed and compared c-myb gene transcriptional regulation using two cell lines modeling normal hematopoietic progenitor cells (HPCs) and transformed myelomonocytic blasts. We report that the transcription factors HoxA9, Meis1, Pbx1 and Pbx2 bind in vivo to the c-myb locus and maintain its expression through different mechanisms in HPCs and leukemic cells. Our analysis also points to a critical role for Pbx2 in deregulating c-myb expression in murine myeloid cells cotransformed by the cooperative activity of HoxA9 and Meis1. This effect is associated with an intronic positioning of epigenetic marks and RNA polymerase II binding in the orthologous region of a previously described alternative promoter for c-myb. Taken together, our results could provide a first hint to explain the abnormal expression of c-myb in leukemic cells.
c-myb; hematopoietic progenitors; myeloid leukemia; Hox and TALE proteins
Background. Oseltamivir resistance in A(H1N1)pdm09 influenza is rare, particularly in untreated community cases. Sustained community transmission has not previously been reported.
Methods. Influenza specimens from the Asia–Pacific region were collected through sentinel surveillance, hospital, and general practitioner networks. Clinical and epidemiological information was collected on patients infected with oseltamivir-resistant viruses.
Results. Twenty-nine (15%) of 191 A(H1N1)pdm09 viruses collected between May and September 2011 from Hunter New England (HNE), Australia, contained the H275Y neuraminidase substitution responsible for oseltamivir resistance. Only 1 patient had received oseltamivir before specimen collection. The resistant strains were genetically very closely related, suggesting the spread of a single variant. Ninety percent of cases lived within 50 kilometers. Three genetically similar oseltamivir-resistant variants were detected outside of HNE, including 1 strain from Perth, approximately 4000 kilometers away. Computational analysis predicted that neuraminidase substitutions V241I, N369K, and N386S in these viruses may offset the destabilizing effect of the H275Y substitution.
Conclusions This cluster represents the first widespread community transmission of H275Y oseltamivir-resistant A(H1N1)pdm09 influenza. These cases and data on potential permissive mutations suggest that currently circulating A(H1N1)pdm09 viruses retain viral fitness in the presence of the H275Y mutation and that widespread emergence of oseltamivir-resistant strains may now be more likely.
The post-implantation syndrome after endovascular aneurysm repair (EVAR) is increasingly recognised. However, when non-vascular trainees are responsible for the care of these patients out of hours, many are investigated if pyrexial. This study assesses the role of microbiological investigations in pyrexia after endovascular aneurysm repair.
PATIENTS AND METHODS
The notes of 75 EVAR patients were reviewed retrospectively. The incidence of postoperative pyrexia and infective complications were calculated and the result of any cultures obtained.
Overall, 58 (77.3%) patients were pyrexial with 48 h of stent insertion. Twenty-four had blood cultures and 12 had urine cultures taken within 48 h of surgery. All of these cultures were negative. However, of those with a pyrexia after 48 h, one of nine blood cultures and two of 11 urine cultures grew organisms. Five pyrexial patients and one apyrexial patient developed a wound infection (a non-significant difference, P = 1.00).
Pyrexia within 48 h of EVAR is common. Microbiological investigation in the first 48 h in these patients is unrewarding. After 48 h, cultures are more likely to show growth. Although each patient must be assessed clinically for signs of sepsis, blood and urine cultures within 48 h of EVAR are generally unnecessary.
Endovascular aneurysm repair (EVAR); Pyrexia; Culture; Infection
Background & objectives:
Information available on HIV-2 and dual infection (HIV-1/2) is limited. This study was carried out among HIV positive individuals in an urban referral clinic in Khar, Mumbai, India, to report on relative proportions of HIV-1, HIV-2 and HIV-1/2 and baseline characteristics, response to and outcomes on antiretroviral treatment (ART).
Retrospective analysis of programme data (May 2006-May 2009) at Khar HIV/AIDS clinic at Mumbai, India was done. Three test algorithm was used to diagnose HIV-1 and -2 infection. Standard ART was given to infected individuals. Information was collected on standardized forms.
A total of 524 individuals (male=51%; median age=37 yr) were included in the analysis over a 3 year period (2006-2009) - 489 (93%) with HIV-1, 28 (6%) with HIV-2 and 7(1%) with dual HIV-1/2 infection. HIV-2 individuals were significantly older than HIV-1 individuals (P<0.001). A significantly higher proportion of HIV-2 patients and those with dual infections had CD4 counts <200 cells/µl compared to HIV-1. HIV-2 individuals were more likely to present in WHO Clinical Stage 4. Of the 443 patients who were started on ART, 358 (81%) were still alive and on ART, 38 (8.5%) died and 3 were transferred out. CD4 count recovery at 6 and 12 months was satisfactory for HIV-1 and HIV-2 patients on protease inhibitor based regimens while this was significantly lower in HIV-2 individuals receiving 3 nucleoside reverse transcriptase inhibitors.
Interpretation & conclusions:
In an urban HIV clinic in Mumbai, India, HIV-2 and dual infections are not uncommon. Adaptation of the current national diagnostic and management protocols to include discriminatory testing for HIV types and providing access to appropriate and effective ART regimens will prevent the development of viral resistance and preserve future therapeutic options.
ART; HIV-1; HIV-2; Mumbai; treatment outcomes
Images in cardiology
In order to investigate the replication timing properties of PCDH11X and PCDH11Y, a pair of protocadherin genes located in the hominid-specific non-pseudoautosomal homologous region Xq21.3/Yp11.2, we conducted a FISH-based comparative study in different human and non-human primate (Gorilla gorilla) cell types. The replication profiles of three genes from different regions of chromosome X (ZFX, XIST and ATRX) were used as terms of reference. Particular emphasis was given to the evaluation of allelic replication asynchrony in relation to the inactivation status of each gene. The human cell types analysed include neuronal cells and ICF syndrome cells, considered to be a model system for the study of X inactivation. PCDH11 appeared to be generally characterized by replication asynchrony in both male and female cells, and no significant differences were observed between human and gorilla, in which this gene lacks X-Y homologous status. However, in differentiated human neuroblastoma and cerebral cortical cells PCDH11X replication profile showed a significant shift towards allelic synchrony. Our data are relevant to the complex relationship between X-inactivation, as a chromosome-wide phenomenon, and asynchrony of replication and expression status of single genes on chromosome X.
PCDH11X/Y; replication asynchrony; replication timing; X-inactivation; Xq21.3/Yp11.2 homology block
terrorism; road crash mortality
climate change; fuel
Methods: Data on deaths from international terrorism (US State Department database) were collated (1994–2003) and compared to the road injury deaths (year 2000 and 2001 data) from the OECD International Road Transport Accident Database.
Results: In the 29 OECD countries for which comparable data were available, the annual average death rate from road injury was approximately 390 times that from international terrorism. The ratio of annual road to international terrorism deaths (averaged over 10 years) was lowest for the United States at 142 times. In 2001, road crash deaths in the US were equal to those from a September 11 attack every 26 days.
Conclusions: There is a large difference in the magnitude of these two causes of deaths from injury. Policy makers need to be aware of this when allocating resources to preventing these two avoidable causes of mortality.
Methods: Monthly Quitline call data and calls within one hour of a television commercial (TVC) being shown were analysed for the 2002–2003 period. Data on target audience rating points (TARPs) and expenditure on TVCs were also used (n = 2319 TVC placements).
Results: Māori were found to register with the Quitline at higher rates during the most intense six campaign months (15% more registrations compared to less intense months). The most effective campaign generated 115 calls per 100 TARPs by Māori callers within one hour of TVC airing (the "Every cigarette" campaign). A more Māori orientated campaign with both health and cultural themes generated 91 calls per 100 TARPs from Māori callers. For these two campaigns combined, the advertising cost per new registration with the Quitline by a Māori caller was $NZ30–48. Two second hand smoke campaigns that did not show the Quitline number were much less effective at 25 and 45 calls per 100 TARPs.
Conclusions: These television advertising campaigns were effective and cost effective in generating calls to a national Quitline by Māori. Health authorities should continue to explore the use of both "threat appeal" style media campaigns and culturally appropriate campaigns to support Quitline use by indigenous peoples.
In the event of an influenza pandemic, the most probable way in which the virus would be introduced to an isolated geographical area is by an infected traveller. We use a mathematical model, structured on the location at which infection occurs and based on published parameters for influenza, to describe an epidemic in a community of one million people. The model is then modified to reflect a variety of control strategies based on social distancing measures, targeted antiviral treatment and antiviral prophylaxis and home quarantine, and the effectiveness of the strategies is compared. The results suggest that the only single strategy that would be successful in preventing an epidemic (with R0=2.0) is targeted antiviral treatment and prophylaxis, and that closing schools combined with either closing work places or home quarantine would only prevent such an epidemic if these strategies were combined with a modest level of antiviral coverage.
mathematical epidemiology; infectious diseases; exotic infections; pandemic influenza
Objective: To estimate the loss of life expectancy attributable to tobacco taxation (via financial hardship and flow-on health effect) in New Zealand.
Design: Data were used on the gradients in life expectancy and smoking by neighbourhood socioeconomic deprivation and survey data on tobacco expenditure. Three estimates were modelled of the percentage of the crude association of neighbourhood deprivation with life expectancy that might be mediated via financial hardship: 100%, 50%, and 25% (best estimate). From this information the impact of tobacco taxation on life expectancy was estimated.
Main results: For the total population, the estimated loss of life expectancy due to tobacco tax ranged from 0.005 years to 0.027 years. For people living in the most deprived 30% of neighbourhoods, the range was 0.009 to 0.044 years (that is, 3 to 16 days of lost life expectancy). For the total population the loss of life expectancy attributable to tobacco tax ranged from 119 to 460 times less than that attributable to deprivation. The loss of life expectancy attributable to tobacco tax was 42 to 257 times less than that attributable to smoking.
Conclusions: The estimated harm to life expectancy from tobacco taxation (via financial hardship) is orders of magnitude smaller than the harm from smoking. Although the analyses involve a number of simplistic assumptions, this conclusion is likely to be robust. Policy makers should be reassured that tobacco taxation is likely to be achieving far more benefit than harm in the general population and in socioeconomically deprived populations.
Methods: A compact disc produced by the National Portrait Gallery in London, UK, was systematically searched for artworks produced in the years 1950 to 1999. A "smoking portrayal" in an artwork was defined as having a cigarette, cigar or pipe in the mouth or hand of a named individual.
Results: Out of 1063 artworks included in the analysis, 53 portrayed smoking by identifiable individuals (5.0%). The rate of portrayal was highest in the 1950s (10%) and 1960s (11%) and then declined sharply thereafter (p value for trend < 0.00001). Smoking virtually disappeared from portraiture in the 1990s (at 0.6%). The median age of the smokers portrayed was significantly higher in the 1970 to 1999 period when compared to the 1950 to 1969 period.
Conclusions: The decline of smoking in this collection of portraiture is consistent with the decline in smoking in the UK over these decades, but contrasts with trends for increasing smoking portrayal described elsewhere for film and television.
Methods: Thirty two children of median age 12.0 years (interquartile range (IQR) 9.5–13.4) with stable asthma were recruited. They underwent spirometric testing, exhaled nitric oxide (eNO) measurement, sputum induction for differential cell count, and ambulatory cough monitoring over 17 hours and 40 minutes. Coughing episodes were counted both as individual spikes and as clusters.
Results: Complete cough frequency data were available in 29 children (90%) and their median forced expiratory volume in 1 second (FEV1) and eNO were 88.5% (IQR 79.5–98) and 23.9 ppb (IQR 11.4–41.5), respectively. The median number of cough episodes was 14 (IQR 7.0–24.0) which was significantly higher than that of normal children (6.7 (IQR 4.1–10.5), p<0.001). Sputum induction was successful in 61% of the subjects; the median induced sputum eosinophil count was 0.05% (IQR 0–9.0). Cough frequency was found to have a significant positive correlation with eNO (Spearman's r =0.781, p<0.001) but not with FEV1 or sputum eosinophil count (r =-0.270, p=0.157; r =0.173, p=0.508, respectively).
Conclusions: Children with stable asthma have increased cough frequency compared with normal controls and cough frequency was greater during the day than at night. Cough may be a more sensitive marker of airway inflammation than simple spirometry.
Objective: To examine the role of tobacco use in creating financial hardship for New Zealand (NZ) low income households with children.
Data: The 1996 NZ census (smoking prevalence by household types), Statistics NZ (household spending surveys 1988-98), and NZ Customs (tobacco released from bond 1988-98).
Main outcome measures: Proportion of children in households with smokers and ≤$NZ15 000 gross income per adult. Proportion of spending on tobacco of second lowest equivalised household disposable income decile and of solo parent households.
Results: In ≤$NZ15 000 gross income per adult households with both children and smokers, there were over 90 000 children, or 11% of the total population aged less than 15 years. Enabling second lowest income decile households with smokers to be smoker-free would on average allow an estimated 14% of the non-housing budgets of those households to be reallocated.
Conclusions: The children in low income households with smokers need to be protected from the financial hardship caused by tobacco use. This protection could take the form of more comprehensive government support for such households and stronger tobacco control programmes. A reliance on tobacco price policy alone to deter smokers is likely to have mixed outcomes—for example, increased hardship among some of these households. The challenge for tobacco control is to move from a sole focus on "doing good" towards incorporating the principle of "doing no harm".